Genetic Variant GABRB1:c.*304dupT (chr4-47426318-C-CT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000812.4(GABRB1):c.*304dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0478 in 213,426 control chromosomes in the GnomAD database, including 279 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.052 ( 214 hom., cov: 29)

Exomes 𝑓: 0.038 ( 65 hom. )

Consequence

GABRB1
NM_000812.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.139

Publications

4 publications found

Variant links:

Genes affected

GABRB1 (HGNC:4081): (gamma-aminobutyric acid type A receptor subunit beta1) The gamma-aminobutyric acid (GABA) A receptor is a multisubunit chloride channel that mediates the fastest inhibitory synaptic transmission in the central nervous system. This gene encodes GABA A receptor, beta 1 subunit. It is mapped to chromosome 4p12 in a cluster comprised of genes encoding alpha 4, alpha 2 and gamma 1 subunits of the GABA A receptor. Alteration of this gene is implicated in the pathogenetics of schizophrenia. [provided by RefSeq, Jul 2008]

GABRB1 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 45
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

GABRB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	NM_000812.4	MANE Select	c.*304dupT		3_prime_UTR	Exon 9 of 9	NP_000803.2	X5DNL6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABRB1	ENST00000295454.8	TSL:1 MANE Select	c.*304dupT		3_prime_UTR	Exon 9 of 9	ENSP00000295454.3	P18505-1

Frequencies

GnomAD3 genomes

AF:

0.0519

AC:

7821

AN:

150622

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0684

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0678

Gnomad EAS

AF:

0.0967

Gnomad SAS

AF:

0.0755

Gnomad FIN

AF:

0.0363

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.0424

Gnomad OTH

AF:

0.0606

GnomAD4 exome

AF:

0.0377

AC:

2363

AN:

62684

Hom.:

Cov.:

AF XY:

0.0384

AC XY:

1219

AN XY:

31782

show subpopulations

African (AFR)

AF:

0.0500

AC:

129

AN:

2578

American (AMR)

AF:

0.0207

AC:

AN:

1930

Ashkenazi Jewish (ASJ)

AF:

0.0481

AC:

136

AN:

2830

East Asian (EAS)

AF:

0.0572

AC:

298

AN:

5210

South Asian (SAS)

AF:

0.0568

AC:

AN:

704

European-Finnish (FIN)

AF:

0.0237

AC:

AN:

2748

Middle Eastern (MID)

AF:

0.0690

AC:

AN:

348

European-Non Finnish (NFE)

AF:

0.0348

AC:

1459

AN:

41926

Other (OTH)

AF:

0.0390

AC:

172

AN:

4410

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

114

228

342

456

570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0520

AC:

7834

AN:

150742

Hom.:

214

Cov.:

AF XY:

0.0508

AC XY:

3734

AN XY:

73534

show subpopulations

African (AFR)

AF:

0.0687

AC:

2820

AN:

41060

American (AMR)

AF:

0.0343

AC:

516

AN:

15044

Ashkenazi Jewish (ASJ)

AF:

0.0678

AC:

235

AN:

3468

East Asian (EAS)

AF:

0.0965

AC:

490

AN:

5078

South Asian (SAS)

AF:

0.0760

AC:

364

AN:

4790

European-Finnish (FIN)

AF:

0.0363

AC:

369

AN:

10164

Middle Eastern (MID)

AF:

0.138

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0424

AC:

2874

AN:

67850

Other (OTH)

AF:

0.0604

AC:

126

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

372

745

1117

1490

1862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0475

Hom.:

Asia WGS

AF:

0.106

AC:

368

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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4-47426318-CT-CTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over